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Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor
Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated lut...
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| Published in: | Hormones and behavior 2020-02, Vol.118, p.104590-104590, Article 104590 |
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| creator | Bohm-Levine, Nathaniel Goldberg, Alexander R. Mariani, Monica Frankfurt, Maya Thornton, Janice |
| description | Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.
•Estradiol improved spatial memory in ovx rats and ANA-12, a brain-derived neurotrophic factor (BDNF) receptor antagonist, blocked this improvement•Lowering Luteinizing Hormone using Antide enhanced spatial memory in ovariectomized rats and ANA-12 blocked this spatial memory improvement•Both Antide and estradiol increased levels of immunoreactive BDNF in the hippocampus.•Neither Antide nor estradiol increased spine density in the hippocampal CA1 region |
| doi_str_mv | 10.1016/j.yhbeh.2019.104590 |
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•Estradiol improved spatial memory in ovx rats and ANA-12, a brain-derived neurotrophic factor (BDNF) receptor antagonist, blocked this improvement•Lowering Luteinizing Hormone using Antide enhanced spatial memory in ovariectomized rats and ANA-12 blocked this spatial memory improvement•Both Antide and estradiol increased levels of immunoreactive BDNF in the hippocampus.•Neither Antide nor estradiol increased spine density in the hippocampal CA1 region</description><identifier>ISSN: 0018-506X</identifier><identifier>EISSN: 1095-6867</identifier><identifier>DOI: 10.1016/j.yhbeh.2019.104590</identifier><identifier>PMID: 31593698</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer's disease ; Brain-derived neurotrophic factor ; Estrogen ; Luteinizing hormone ; Spatial memory</subject><ispartof>Hormones and behavior, 2020-02, Vol.118, p.104590-104590, Article 104590</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-2e93341f0670c0101b42a17c18e9aada284302091278355c30f222cbb278091e3</citedby><cites>FETCH-LOGICAL-c359t-2e93341f0670c0101b42a17c18e9aada284302091278355c30f222cbb278091e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31593698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bohm-Levine, Nathaniel</creatorcontrib><creatorcontrib>Goldberg, Alexander R.</creatorcontrib><creatorcontrib>Mariani, Monica</creatorcontrib><creatorcontrib>Frankfurt, Maya</creatorcontrib><creatorcontrib>Thornton, Janice</creatorcontrib><title>Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor</title><title>Hormones and behavior</title><addtitle>Horm Behav</addtitle><description>Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.
•Estradiol improved spatial memory in ovx rats and ANA-12, a brain-derived neurotrophic factor (BDNF) receptor antagonist, blocked this improvement•Lowering Luteinizing Hormone using Antide enhanced spatial memory in ovariectomized rats and ANA-12 blocked this spatial memory improvement•Both Antide and estradiol increased levels of immunoreactive BDNF in the hippocampus.•Neither Antide nor estradiol increased spine density in the hippocampal CA1 region</description><subject>Alzheimer's disease</subject><subject>Brain-derived neurotrophic factor</subject><subject>Estrogen</subject><subject>Luteinizing hormone</subject><subject>Spatial memory</subject><issn>0018-506X</issn><issn>1095-6867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kM-L1DAUx4O4OOOuf4EgOXrp-JK0nUbwIIuuwsDKorC3kKavToa2GV_aQr3tf74ZZ_Xo5f3i-359GHstYCNAlO8Om2Vf434jQehUyQsNz9hagC6ysiq3z9kaQFRZAeX9ir2M8ZBSUeT5C7ZSotCq1NWaPdxhMzk__OTdNKIf_O9TvA_UhwF5hzN2kdt2ROJhtuTRjaFfuO-PFGaMPB7t6G3He-wDLe_5txCjrzvkFJIJLa_J-iFrkPyMDR9wojBSOO69461Nw-iKXbS2i_jqyV-yH58_fb_-ku1ub75ef9xlThV6zCRqpXLRQrkFBwlAnUsrtk5UqK1trKxyBRK0kNtKFYVT0EopXV2nPFVRXbK357np8l8TxtH0PjrsOjtgmKKRCpSEqix1kqqz1FF6h7A1R_K9pcUIMCf25mD-sDcn9ubMPnW9eVow1T02_3r-wk6CD2dBYoqzRzLReRwcNp4SV9ME_98Fj2S2mEI</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Bohm-Levine, Nathaniel</creator><creator>Goldberg, Alexander R.</creator><creator>Mariani, Monica</creator><creator>Frankfurt, Maya</creator><creator>Thornton, Janice</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202002</creationdate><title>Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor</title><author>Bohm-Levine, Nathaniel ; Goldberg, Alexander R. ; Mariani, Monica ; Frankfurt, Maya ; Thornton, Janice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-2e93341f0670c0101b42a17c18e9aada284302091278355c30f222cbb278091e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alzheimer's disease</topic><topic>Brain-derived neurotrophic factor</topic><topic>Estrogen</topic><topic>Luteinizing hormone</topic><topic>Spatial memory</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bohm-Levine, Nathaniel</creatorcontrib><creatorcontrib>Goldberg, Alexander R.</creatorcontrib><creatorcontrib>Mariani, Monica</creatorcontrib><creatorcontrib>Frankfurt, Maya</creatorcontrib><creatorcontrib>Thornton, Janice</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hormones and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bohm-Levine, Nathaniel</au><au>Goldberg, Alexander R.</au><au>Mariani, Monica</au><au>Frankfurt, Maya</au><au>Thornton, Janice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor</atitle><jtitle>Hormones and behavior</jtitle><addtitle>Horm Behav</addtitle><date>2020-02</date><risdate>2020</risdate><volume>118</volume><spage>104590</spage><epage>104590</epage><pages>104590-104590</pages><artnum>104590</artnum><issn>0018-506X</issn><eissn>1095-6867</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.
•Estradiol improved spatial memory in ovx rats and ANA-12, a brain-derived neurotrophic factor (BDNF) receptor antagonist, blocked this improvement•Lowering Luteinizing Hormone using Antide enhanced spatial memory in ovariectomized rats and ANA-12 blocked this spatial memory improvement•Both Antide and estradiol increased levels of immunoreactive BDNF in the hippocampus.•Neither Antide nor estradiol increased spine density in the hippocampal CA1 region</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31593698</pmid><doi>10.1016/j.yhbeh.2019.104590</doi><tpages>1</tpages></addata></record> |
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| subjects | Alzheimer's disease Brain-derived neurotrophic factor Estrogen Luteinizing hormone Spatial memory |
| title | Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor |
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